权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The effect of beta-stimulants on mua channels in the frog ventrieular cells

β-兴奋剂对青蛙心室细胞 mua 通道的影响

基本信息

批准号：
01570065
负责人：
SEYAMA Issei
金额：
$ 1.34万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

This experiment was designed to study the commitment of A-kinase system in the regulation of Na channel functions in the frog ventricular cells. The voltage clamp method using oilgap method was used to improve the spatical control of the membrane potential. 10 u M propranolol, beta-stimulant, does not change the transient membrane current through Na channel, I_<Na>, neither does so another stimulant, histamine. Forskoline, direct stimulant to adenylate cyclase, also fails to affect it. There are several reports that beta-stimulant suppressed I_<Na> via A-kinase system in the mammalian ventricular cells. One of the most serious problems in studying the change in INa for a long time is the shift of the voltage-dependency of inactivation process to the hyperpolarizing direction. This shift may spuriously produce a change in I_<Na> similar to those reported. Care was exercis in selecting the preparasions which do not produce the shift, comparing the inactivation curve before and after the … More stimulation of A-kinase system. Other concerning point is the expermental method. Because half of the cell membrane of a single cell is disrupted, critical malerials may be washied out from the intracellular phase, leading to an artificial loss of the control of channel. I have negated this possibility by confirming that beta-stimulant only enhances current through Ca channel, I_<Ca> in the experimental condition in which both I_<Na> and I_<Ca> are functioning. In spite of the conservative property in the amino acid sequence of the critical part of the Na channel, differdnce in the sensiivity of Na channel to mu-conotoxin between the skeletal and the nerve cells suggests a subtle change in molecular configuration. Thus, distinction of the response of Na channel to beta-stimulant may be due to differince in species. There remains possibility that this is due to an artifact, because the experimental condition in the mammalian preparatins is very strict and the extent of suppression of I_<Na> reported is very limited. All these experimental findings lead me to the conclusion that Na channels in the frog ventricular cells are not regulated by A-kinase systms. Less

本实验旨在研究A-激酶系统在青蛙心室肌细胞钠通道功能调节中的作用。为改善膜电位的空间控制，采用了基于油隙的电压钳位法。10uM的心得安不改变钠通道的瞬时膜电流，组胺也不改变。腺苷环化酶的直接刺激剂Forskoline也不能影响它。有报道称，β-受体激动剂通过A-激酶系统抑制哺乳动物心肌细胞内的I_1、Na、GT。长期以来研究INA变化最严重的问题之一是失活过程的电压依赖性向超极化方向的转变。这种转变可能会虚假地导致I_&lt；Na&>；的变化，类似于报道的变化。仔细选择不产生移位的准备，比较…前后的失活曲线对A-激酶系统有更多的刺激。另一个值得关注的问题是实验方法。由于单个细胞一半的细胞膜被破坏，关键的恶性物质可能被从细胞内相洗掉，导致人为地失去对通道的控制。我已经否认了这种可能性，证实了在实验条件下，β-兴奋剂只增强了通过钙通道的电流，在实验条件下，I_lt；Na&gt；和I_lt；Ca&gt；都在起作用。尽管钠通道关键部分的氨基酸序列具有保守性，但骨骼细胞和神经细胞对魔芋毒素的敏感性不同，提示其分子构型发生了微妙的变化。因此，钠通道对β-兴奋剂反应的差异可能是由于物种的不同。这仍然有可能是由于人工制品，因为在哺乳动物制备中的实验条件非常严格，而且已报道的对I_&lt；Na&gt；的抑制程度非常有限。所有这些实验结果使我得出结论，青蛙心室肌细胞的钠通道不受A-激酶系统的调节。较少